title: Quantum chemical study of the enzymatic repair of T(6-4)C/C(6-4)T UV-photolesions by DNA photolyases.
abstract: Several strategies have evolved to repair one of the abundant UV radiation-induced damages caused to DNA, namely the mutagenic pyrimidine (6-4) pyrimidone photolesions. DNA (6-4)-photolyases are enzymes repairing these lesions by a photoinitiated electron transfer. An important aspect of a possible repair mechanism is its generality and transferability to different (6-4) lesions. Therefore, previously suggested mechanisms for the repair of the T(6-4)T lesion are here transferred to the T(6-4)C and C(6-4)T lesions and investigated theoretically using quantum chemical methods. Despite the different functional groups of the pyrimidine bases involved, a general valid molecular mechanism was identified, in which the initial step is an electron transfer coupled to a proton transfer from the protonated HIS365 to the N3(') nitrogen of the 3(') pyrimidine, followed by an intramolecular OH/NH2 transfer in one concerted step, which does not require an oxetane/azetidine or isolated water/ammonia intermediate.
authors.affiliation: Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany. shirin.faraji@uni-heidelberg.de
authors.forename: Shirin
authors.initials: S
authors.lastname: Faraji
authors.forename: Lukas
authors.initials: L
authors.lastname: Wirz
authors.forename: Andreas
authors.initials: A
authors.lastname: Dreuw
mesh_terms: D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D008958:Models, Molecular; D011740:Pyrimidine Dimers / Q000737:chemistry; D011789:Quantum Theory; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D003596:Cytosine; D004247:DNA; D004255:Deoxyribodipyrimidine Photo-Lyase; D013941:Thymine
keywords: DNA cleavage; DNA repair; electron transfer; photolyases; quantum chemical calculations